Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
To assess the effect of routine doses of ibuprofen on post-partum blood pressure control in women with gestational hypertension (gHTN) or preeclampsia without severe features (preE).
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for post-partum analgesia. This use is supported by limited data on post-partum pain specifically; however, ibuprofen and other NSAIDs are superior to acetaminophen in ameliorating uterine pain and cramping in dysmenorrhea. The effect of NSAIDs on blood pressure (BP) in women post-partum is less well-known. In non-pregnant hypertensive patients NSAIDs are associated with increased BP over short courses of days to months, though effects of various NSAIDs differ. Pooled analyses suggest changes in mean BP of up to 3-6 mm Hg depending on the measurement method.There are case reports of hypertensive crises after NSAID administration post-partum in both normotensive and hypertensive women. A larger, recent retrospective cohort study found no difference in mean arterial pressure (MAP) or need for antihypertensive therapy in women with severe hypertensive disorders of pregnancy who were exposed to NSAIDs post-partum.
In light of the potential for worsening blood pressure in women with hypertensive disorders of pregnancy, the Task Force on Hypertension in Pregnancy of American College of Obstetricians and Gynecologists stated that "providers should be reminded of the contribution of nonsteroidal anti-inflammatory agents to increased BP." Additionally the task force recommends that NSAIDS "be replaced by other analgesics in women with hypertension that persists for more than 1 day postpartum". However, provider practices since the publication of these guidelines have varied.
Hypothesis: When compared to acetaminophen, ibuprofen does not increase post-partum systolic blood pressure (SBP) above baseline to a clinically relevant degree (≥10 mmHg) in women with gHTN and preE.
Aim 1: To assess the mean difference in SBP during 24 hours of exposure to ibuprofen and acetaminophen.
Aim 2: To assess whether ibuprofen results in higher satisfaction with pain control in the immediate post-partum period (48 hours) compared to acetaminophen.
Aim 3: To prospectively assess the need for post-partum anti-hypertensive therapy and readmission for blood pressure control in women with gHTN and preE. The post-partum period is defined as delivery through 6 weeks after delivery.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ibuprofen followed by acetaminophen | Active Comparator | Ibuprofen administered immediately post-partum, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours followed by acetaminophen, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours. |
|
| Acetaminophen followed by ibuprofen | Active Comparator | Acetaminophen administered immediately post-partum, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours followed by ibuprofen, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ibuprofen | Drug | At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with ibuprofen followed by acetaminophen. |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in Systolic Blood Pressure (SBP) | The adjusted mean difference in systolic blood pressure after 24 hours of exposure each to ibuprofen and acetaminophen. | 24 hours following intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Self-reported Pain Score 2 Hours After First Intervention | Prior to the first dose of pain medication, participants will take a brief, self-administered survey to assess abdominal and overall pain using a 0-10 scale. Two hours after the first dose of study drug, participants will repeat the self-administered survey to assess abdominal, perineal, and overall pain using a 0-10 scale. Clinical Pain Scale: 0=no pain to 10=worst pain. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Jourdan Triebwasser, MD | University of Michigan | Principal Investigator |
| Elizabeth Langen, MD | University of Michigan | Principal Investigator |
| Alexander Tsodikov, PhD | University of Michigan | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
74 women were consented prior to delivery.
Women were subsequently excluded due to cesarean delivery (n=20), severe features of preeclampsia (n=7), additional anesthesia (n=2), and delivery physician preference (n=2).
43 women were randomized. Six women declined study medication and were not included in intention-to-treat analysis.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Ibuprofen Followed by Acetaminophen | Period 1: Ibuprofen 600 mg every 6 hours for 24 hours Period 2: Acetaminophen 650 mg every 6 hours for 24 hours. No washout |
| FG001 | Acetaminophen Followed by Ibuprofen | Period 1: Acetaminophen 650 mg every 6 hours for 24 hours Period 2: Ibuprofen 600 mg every 6 hours for 24 hours. No washout |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (24 Hours) |
|
| ||||||||||||||||||||||||
| Second Intervention (24 Hours) |
|
Baseline characteristics were measured after the first milestone, after 6 total participants who were initially randomized declined the study medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Ibuprofen Followed by Acetaminophen | Ibuprofen administered immediately post-partum, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours followed by acetaminophen, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours. Ibuprofen: At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with ibuprofen followed by acetaminophen. Acetaminophen: At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with acetaminophen followed by ibuprofen. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Difference in Systolic Blood Pressure (SBP) | The adjusted mean difference in systolic blood pressure after 24 hours of exposure each to ibuprofen and acetaminophen. | 37 women who received >=1 dose of study drug were included in intention-to-treat analyses. 35 women had blood pressure recorded in the intended ibuprofen period; 2 excluded due to discharge prior to cross-over. 36 women had blood pressure recorded in the intended acetaminophen period; 1 excluded with no blood pressure measured after cross-over. | Posted | Mean | Standard Deviation | mmHg | 24 hours following intervention |
|
48 hours
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ibuprofen | Women who received ibuprofen intervention | 0 |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Elizabeth Langen | University of Michigan | 734-764-3406 | elangen@med.umich.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 10, 2017 | Mar 12, 2019 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D046110 | Hypertension, Pregnancy-Induced |
| D011225 | Pre-Eclampsia |
| D000377 | Agnosia |
| ID | Term |
|---|---|
| D011248 | Pregnancy Complications |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D006973 | Hypertension |
Not provided
Not provided
| ID | Term |
|---|---|
| D007052 | Ibuprofen |
| D000082 | Acetaminophen |
| ID | Term |
|---|---|
| D010666 | Phenylpropionates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Acetaminophen | Drug | At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with acetaminophen followed by ibuprofen. |
|
|
| At the time of first dose of study drug and 2 hours after |
| Mean Pain Score by Nursing Assessment | Pain scores using a 0-10 scale as assessed by nursing during the 48 hours from initial study medication administration will be abstracted from the participant's medical record. Clinical Pain Scale: 0=no pain to 10=worst pain. All pain scores during the first intervention (0-24 hours) and second intervention (24-48) are included according to intention-to-treat principles. | 0-24 hours and 24-48 hours after initial study medication administration |
| Satisfaction With Pain Control During 24 Hours of Exposure Each to Ibuprofen and Acetaminophen | A brief survey on satisfaction with pain control during the first 24 hours post-partum and the second 24 hours post-partum, as well as overall during post-partum stay will be administered prior to discharge using a 1-5 Likert scale: 1=not satisfied to 5=extremely satisfied. | 24 hours and 48 hours after initial study medication administration |
| Withdrew after receiving study drug |
|
| NOT COMPLETED |
|
|
| BG001 | Acetaminophen Followed by Ibuprofen | Acetaminophen administered immediately post-partum, 650 mg (2 x 325 mg tablets) every 6 hours for 24 hours followed by ibuprofen, 600 mg (3 x 200 mg tablets) every 6 hours for 24 hours. Ibuprofen: At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with ibuprofen followed by acetaminophen. Acetaminophen: At the time of delivery, eligibility will be reviewed. If the participant remains eligible, she will be randomized by the study pharmacy to begin post-partum analgesic therapy with acetaminophen followed by ibuprofen. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| BMI | Median | Inter-Quartile Range | kg/m^2 |
|
| Marital Status | Count of Participants | Participants |
|
| Insurance | Count of Participants | Participants |
|
| Nulliparous | Count of Participants | Participants |
|
| Gestational Age | Mean | Standard Deviation | weeks |
|
| Gestational Hypertension | Count of Participants | Participants |
|
| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Maximum Systolic Blood Pressure Prior to Delivery | The maximum systolic blood pressure between admission and delivery for each participant was recorded. The mean of the maximum systolic blood pressures was calculated for each group. | Mean | Standard Deviation | mmHg |
|
| OG001 | Acetaminophen | Intention to treat population: received at least 1 dose of study medication in the first intervention period (either ibuprofen or acetaminophen), and had a blood pressure measured during the intended acetaminophen period. |
|
|
|
| Secondary | Change in Self-reported Pain Score 2 Hours After First Intervention | Prior to the first dose of pain medication, participants will take a brief, self-administered survey to assess abdominal and overall pain using a 0-10 scale. Two hours after the first dose of study drug, participants will repeat the self-administered survey to assess abdominal, perineal, and overall pain using a 0-10 scale. Clinical Pain Scale: 0=no pain to 10=worst pain. | 14 women in the ibuprofen first group and 8 women in the the acetaminophen first group completed pain surveys before and 2 hours after 1st dose of study drug. | Posted | Mean | Standard Deviation | score on a scale | At the time of first dose of study drug and 2 hours after |
|
|
|
|
| Secondary | Mean Pain Score by Nursing Assessment | Pain scores using a 0-10 scale as assessed by nursing during the 48 hours from initial study medication administration will be abstracted from the participant's medical record. Clinical Pain Scale: 0=no pain to 10=worst pain. All pain scores during the first intervention (0-24 hours) and second intervention (24-48) are included according to intention-to-treat principles. | Of 37 women in intention-to-treat analyses, 35 were analyzed in ibuprofen treatment; 2 of those women had no recorded nursing pain score in ibuprofen period (n=33). 36 women were analyzed in acetaminophen treatment, but 1 of those women had no recorded nursing pain score in acetaminophen period (n=35). | Posted | Mean | Standard Deviation | score on a scale | 0-24 hours and 24-48 hours after initial study medication administration |
|
|
|
|
| Secondary | Satisfaction With Pain Control During 24 Hours of Exposure Each to Ibuprofen and Acetaminophen | A brief survey on satisfaction with pain control during the first 24 hours post-partum and the second 24 hours post-partum, as well as overall during post-partum stay will be administered prior to discharge using a 1-5 Likert scale: 1=not satisfied to 5=extremely satisfied. | 11 women in the ibuprofen first group and 6 women in the the acetaminophen first group completed the satisfaction survey prior to discharge. | Posted | Median | Inter-Quartile Range | units on a scale | 24 hours and 48 hours after initial study medication administration |
|
|
|
|
| 29 |
| 0 |
| 29 |
| 0 |
| 29 |
| EG001 | Acetaminophen | Women who received acetaminophen intervention | 0 | 34 | 0 | 34 | 0 | 34 |
Not provided
Not provided
Not provided
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010468 | Perceptual Disorders |
| D019954 | Neurobehavioral Manifestations |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000083 |
| Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| Overall pain |
|
| 0.91 |
Perineal pain |
| Superiority |
| Change in overall pain | t-test, 2 sided | 0.88 | Overall pain | Superiority |
| Overall |
|
| 0.06 |
| Superiority |
| Overall satisfaction with pain control during study period | Wilcoxon (Mann-Whitney) | 0.04 | Superiority |